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Dermcidin: a novel human antibiotic peptide secreted by sweat glands

Nature Immunology volume 2, pages 1133–1137 (2001)Cite this article

Abstract

Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47–amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.

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Figure 1: DCD expression was restricted to cells in the skin.
Figure 2: DCD was expressed in human eccrine sweat glands.
Figure 3: DCD was secreted into human sweat.
Figure 4: DCD had antimicrobial activity and was salt- and pH-insensitive.

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GenBank/EMBL/DDBJ

References

  1. Gallo, R. L. et al. Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds. Proc. Natl Acad. Sci. USA 91, 11035–11039 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Harder, J., Bartels, J., Christophers, E. & Schroder, J. M. A peptide antibiotic from human skin. Nature 387, 861 (1997).

    Article  CAS  PubMed  Google Scholar 

  3. Frohm, M. et al. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. J. Biol. Chem. 272, 15258–15263 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Hancock, R. E. & Lehrer, R. Cationic peptides: a new source of antibiotics. Trends Biotechnol. 16, 82–88 (1998).

    Article  CAS  PubMed  Google Scholar 

  5. Jones, D. E. & Bevins, C. L. Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel. FEBS Lett. 315, 187–192 (1993).

    Article  CAS  PubMed  Google Scholar 

  6. Harder, J., Bartels, J., Christophers, E. & Schroder, J. M. Isolation and characterization of Human β-Defensin-3, a novel human inducible peptide antibiotic. J. Biol. Chem. 276, 5707–5713 (2000).

    Article  PubMed  Google Scholar 

  7. Hipfel, R., Schittek, B., Bodingbauer, Y. & Garbe, C. Specifically regulated genes in malignant melanoma tissues identified by subtractive hybridization. Br. J. Cancer 82, 1149–1157 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Todorov, P. et al. Characterization of a cancer cachectic factor. Nature 379, 739–742 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Todorov, P. T., Deacon, M. & Tisdale, M. J. Structural analysis of a tumor-produced sulfated glycoprotein capable of initiating muscle protein degradation. J. Biol. Chem. 272, 12279–12288 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Cunningham, T. J. et al. Identification of a survival-promoting peptide in medium conditioned by oxidatively stressed cell lines of nervous system origin. J. Neurosci. 18, 7047–7060 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. Cunningham, T. J., Jing, H., Wang, Y. & Hodge, L. Calreticulin binding and other biological activities of survival peptide Y-P30 including effects of systemic treatment of rats. Exp. Neurol. 163, 457–468 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Bals, R. Epithelial antimicrobial peptides in host defense against infection. Respir. Res. 1, 141–150 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Valore, E. V. et al. Human β-defensin-1: an antimicrobial peptide of urogenital tissues. J. Clin. Invest. 101, 1633–1642 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sato, K., Kang, W. H., Saga, K. & Sato, K. T. Biology of sweat glands and their disorders. I. Normal sweat gland function. J. Am. Acad. Dermatol. 20, 537–563 (1989).

    Article  CAS  PubMed  Google Scholar 

  15. Okada, T., Konishi, H., Ito, M., Nagura, H. & Asai, J. Identification of secretory immunoglobulin A in human sweat and sweat glands. J. Invest. Dermatol. 90, 648–651 (1988).

    Article  CAS  PubMed  Google Scholar 

  16. Jones, A. P., Webb, L. M., Anderson, A. O., Leonard, E. J. & Rot, A. Normal human sweat contains interleukin-8. J. Leukoc. Biol. 57, 434–437 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Didierjean, L. et al. Biologically active interleukin 1 in human eccrine sweat: site-dependent variations in alpha/beta ratios and stress-induced increased excretion. Cytokine 2, 438–446 (1990).

    Article  CAS  PubMed  Google Scholar 

  18. Ahmed, A. A., Nordlind, K., Schultzberg, M. & Liden, S. Interleukin-1α- and β-, interleukin-6- and tumour necrosis factor-β-like immunoreactivities in chronic granulomatous skin conditions. Acta Derm. Venereol. 74, 435–440 (1994).

    CAS  PubMed  Google Scholar 

  19. Wollina, U. et al. Eccrine sweat glands: expression of transforming growth factor-β and bone morphogenetic protein type I receptors and their intracellular signalling Smad proteins. Acta Derm. Venereol. 79, 183–186 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Myal, Y. et al. The prolactin-inducible protein (PIP/GCDFP-15) gene: cloning, structure and regulation. Mol. Cell. Endocrinol. 80, 165–175 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. Fraki, J. E. Human skin proteases. Separation and characterization of two acid proteases resembling cathepsin B1 and cathepsin D and of an inhibitor of cathepsin B1. Arch. Dermatol. Res. 255, 317–330 (1976).

    Article  CAS  PubMed  Google Scholar 

  22. Fraki, J. E., Jansen, C. T. & Hopsu-Havu, V. K. Human sweat kallikrein. Biochemical demonstration and chromatographic separation from several other esteropeptidases in the sweat. Acta Derm. Venereol. 50, 321–326 (1970).

    CAS  PubMed  Google Scholar 

  23. Goldman, M. J. et al. Human β-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88, 553–560 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Gallo, R. L. & Huttner, K. M. Antimicrobial peptides: an emerging concept in cutaneous biology. J. Invest. Dermatol. 111, 739–743 (1998).

    Article  CAS  PubMed  Google Scholar 

  25. Tossi, A., Sandri, L. & Giangaspero, A. Amphipathic α-helical antimicrobial peptides. Biopolymers 55, 4–30 (2000).

    Article  CAS  PubMed  Google Scholar 

  26. Hancock, R. E. & Lehrer, R. Cationic peptides: a new source of antibiotics. Trends Biotechnol. 16, 82–88 (1998).

    Article  CAS  PubMed  Google Scholar 

  27. Hipfel, R., Garbe, C. & Schittek, B. RNA isolation from human skin tissues for colorimetric differential display. J. Biochem. Biophys. Meth. 37, 131–135 (1998).

    Article  CAS  PubMed  Google Scholar 

  28. Schaumburg-Lever, G. Ultrastructural localization of lectin-binding sites in normal skin. J. Invest. Dermatol. 94, 465–470 (1990).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank T. Iftner and colleagues for DNA sequencing; M. Schwarz and colleagues for the use of radioisotopes and Phosphorimager; B. Fehrenbacher and H. Bischof for electron microscopy; A. Nordheim for mass spectrometry; E. Maczey for technical assistance; and P. Gött, T. Paul, M. Stark and F. Lang for discussions. Supported by the Fortüne-program of the Eberhard-Karls-University Tübingen (432-0-1), the Bundesministerium für Bildung und Forschung (IZKF, Fö01KS9602) and the Deutsche Forschungsgemeinschaft (SFB510).

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Authors and Affiliations

  1. Department of Dermatology, Eberhard-Karls-University Tübingen, Germany

    Birgit Schittek, Rainer Hipfel, Birgit Sauer, Jürgen Bauer, Friedegund Meier, Gernot Rassner & Claus Garbe

  2. Medical and Natural Sciences Research Center, Eberhard-Karls-University Tübingen, Germany

    Hubert Kalbacher

  3. Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany

    Stefan Stevanovic

  4. Department of Molecular Biology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany

    Markus Schirle

  5. Institute of Anthropology and Human Genetics, Eberhard-Karls-University Tübingen, Germany

    Kristina Schroeder & Nikolaus Blin

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Correspondence to Birgit Schittek.

Supplementary information

Web Figure 1.

Sequence of DCD. (a) Full-length cDNA of DCD (458 bp). Exons, positions of introns, start and stop codons are indicated. UTS: untranslated regions. (b) Predicted amino acid sequence of DCD. (GIF 14 kb)

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Schittek, B., Hipfel, R., Sauer, B. et al. Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nat Immunol 2, 1133–1137 (2001). https://doi.org/10.1038/ni732

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